Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events

Henrike O Heyne; Fanny-Dhelia Pajuste; Julian Wanner; Jennifer I Daniel Onwuchekwa; Reedik Mägi; Aarno Palotie; FinnGen; Estonian Biobank research team; Reetta Kälviainen; Mark J Daly

doi:10.1038/s41467-024-50295-z

Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events

Nat Commun. 2024 Jul 25;15(1):6277. doi: 10.1038/s41467-024-50295-z.

Authors

Henrike O Heyne^{1

2

3

4}, Fanny-Dhelia Pajuste^{5

6}, Julian Wanner^{7

8}, Jennifer I Daniel Onwuchekwa^{7

9}, Reedik Mägi^{5

6}, Aarno Palotie^{8

10

11}; FinnGen; Estonian Biobank research team; Reetta Kälviainen^#^{12

13}, Mark J Daly^#^{8

10

11

14}

Affiliations

¹ Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany. [email protected].
² Hasso Plattner Institute, Mount Sinai School of Medicine, New York, NY, US. [email protected].
³ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. [email protected].
⁴ Program for Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
⁵ Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
⁶ Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
⁷ Hasso Plattner Institute for Digital Engineering, University of Potsdam, Potsdam, Germany.
⁸ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
⁹ Faculty of Life Sciences, University of Siegen, Siegen, Germany.
¹⁰ Program for Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹¹ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹² Kuopio Epilepsy Center, Neurocenter, Kuopio University Hospital, Member of ERN EpiCARE, Kuopio, Finland.
¹³ Institute of Clinical Medicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.
¹⁴ Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.

^# Contributed equally.

Abstract

A diagnosis of epilepsy has significant consequences for an individual but is often challenging in clinical practice. Novel biomarkers are thus greatly needed. Here, we investigated how common genetic factors (epilepsy polygenic risk scores, [PRSs]) influence epilepsy risk in detailed longitudinal electronic health records (EHRs) of > 700k Finns and Estonians. We found that a high genetic generalized epilepsy PRS (PRS_GGE) increased risk for genetic generalized epilepsy (GGE) (hazard ratio [HR] 1.73 per PRS_GGE standard deviation [SD]) across lifetime and within 10 years after an unspecified seizure event. The effect of PRS_GGE was significantly larger on idiopathic generalized epilepsies, in females and for earlier epilepsy onset. Analogously, we found significant but more modest focal epilepsy PRS burden associated with non-acquired focal epilepsy (NAFE). Here, we outline the potential of epilepsy specific PRSs to serve as biomarkers after a first seizure event.

MeSH terms

Adolescent
Adult
Aged
Biomarkers
Child
Electronic Health Records
Epilepsies, Partial / genetics
Epilepsy / epidemiology
Epilepsy / genetics
Epilepsy, Generalized* / genetics
Female
Genetic Predisposition to Disease*
Genetic Risk Score
Humans
Longitudinal Studies
Male
Middle Aged
Multifactorial Inheritance* / genetics
Risk Factors
Seizures* / genetics
Young Adult

Polygenic risk scores as a marker for epilepsy risk across lifetime and after unspecified seizure events

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